The proposed Senator Jacob Javits Center will be dedicated to research on the basic neurobiology of the primate neocortex. Although the site of dysfunction in a large share of neurological diseases and human suffering, the neocortex has not been the focus of a specific Institute or of a Center devoted to multidisciplinary research. A team of investigators with wide experience (molecular biology, cell biology, biochemistry, immunocytochemistry, electron microscopy, endocrinology, neuroanatomy, neurophysiology, pharmacology, psychobiology, computer engineering, veterinary medicine, neurosurgery and neuropathology) have joined forces to explore three major themes: [1] Organization, [2] Development, and [3] Modifiability of the neocortex in the rhesus monkey. Each theme will be studied at the molecular, structural, physiological and behavioral levels, and the design of these studies generally will allow the use of the same set of animals for multiple experiments. The first theme includes basic analysis of input-output relationships and microcircuitry of selected cortical areas, their transmitters, receptors and information processing properties. The second theme is built upon the first and includes genetic and epigenetic determinants of (molecular, structural and functional) neuronal phenotypes and development of their laminar, modular and regional positions; studies in this theme will also examine the mode and mechanisms of establishment of axonal connections and the sequence, tempo and pattern of synaptogenesis in selected cortical regions. The third theme concerns the molecular, anatomical and physiological modifiability of neocortex with emphasis on interactions between ipsilateral and contralateral cortico-cortical connections, afferents, cortico-subcortical and intrinsic microcircuitry. The techniques of prenatal neurosurgery will enable experimental manipulation of cortical development, its connections and synaptic organization at critical fetal ages. Studies will be carried out on the rhesus monkey with the intent of enhancing understanding of cellular mechanisms in normal cortical development and pathogenesis of disorders affecting higher cortical functions in humans. The Center will promote research collaboration and enable comprehensive, multipronged and quantitative analyses that have not been possible before now, and that would not be practical for individual investigators supported by separate research grants.